The proposed studies will continue to investigate the influence of hypertonic mannitol on cardiac muscle. Specifically, the research proposed for the future will utilize isolated, isometrically contracting cat papillary muscles; isolated in vitro buffer perfused vascular smooth muscle preparations; isolated, blood perfused canine hearts; anesthetized, open-chest dog preparations and unsedated, closed-chest intact dog models to continue the investigation of mannitol's influence on the heart. The experiments will also attempt to identify the mechanism(s) of mannitol's ability to reduce vascular resistance and increase coronary blood flow in isolated smooth muscle vascular preparations by studying isolated mesenteric and central ear arterial preparation and isolated coronary vascular preparations. Mechanical alterations will be coupled with 45Ca flux measurements in these isolated vascular preparations attempting to better understand the mechanism(s) of mannitol's vasodilator effect. Comparative studies directed at determining how mannitol exerts a different inotropic effect in isolated cardiac muscle from different species will be obtained by further study of isolated rat and cat papillary muscles. Thus, in the coming year of this evaluation the major emphasis will be on a better understanding of mechanisms related to hypertonic mannitol's varied cardiac effects. BIBLIOGRAPHIC REFERENCES: Willerson JT, Watson JT, Platt MR: Effect of hypertonic mannitol and intraaortic counterpulsation on regional myocardial blood flow and ventricular performance in dogs during myocardial ischemia. Am J Cardiol 37:514-519, 1976. Hutton I, Platt M, Watson J, Templeton G, Willerson JT: Influence of frequency of atrial contraction and coronary blood flow and ventricular performance in the conscious dog with myocardial infarction. Cardiovas Res 10:109-118, 1976.